PROJECT SUMMARY/ABSTRACT ? Pilot and Exploratory Studies Core (PESC) The objective of the Pilot/Exploratory Studies Core (PESC) of the Duke OAIC is to conduct high quality Pilot Projects that inform the selection, design, and conduct of subsequent larger, hypothesis-driven research in our theme: to understand and optimize reserve and resilience. The Specific Aims are to: 1) advance top quality science related to late-life reserve and resilience, 2) attract and nurture a diverse cadre of outstanding early investigators in aging research or established investigators pursuing promising new directions related to our theme, and 3) build and sustain relationships with critical stakeholders to maximize the impact and translation of the work conducted through this and future OAICs. By leveraging institutional funding, we will support at least three Pilot Projects per year. We use small exploratory pilot monies as a rapid response mechanism to take advantage of cutting edge areas. The PESC solicits and selects high quality pilot studies from across Duke University Medical Center using a rigorous, multi-stage process that incorporates internal and external review. The PESC carefully monitors study progress and assists in the development of larger grant proposals from pilot study findings. To accomplish our Aims, the Duke PESC includes several highly innovative features: 1) the Pilot Grants Workshop, developed by OAIC Director Kenneth Schmader and frequently requested in national venues, 2) the inclusion of patient/community representatives on the Review Panel selecting pilots, 3) the Data Integration Working Group, which is a central hub for scientific development, oversight, and promoting translation, and 4) mechanisms that support the science and careers of unfunded pilot study applicants. Four Pilot Projects are proposed in the first two years. PES1 investigates the feasibility and efficacy of a pre- operative exercise intervention (?prehabilitation?) to enhance resilience for older adults undergoing elective surgery. PES2 investigates the role of transient receptor potential vanilloid 4 (TRPV4)-mediated mechano- transduction in restoring the reserve capacity of old chondrocytes, potentially improving their ability to withstand physiological load and avoid osteoarthritis. PES3 will demonstrate the effect of aging on autophagy in muscle stem cells and seek specific mechanistic targets for enhancing muscle reserve and reducing sarcopenia. PES4 incorporates clinical and biological data to develop clinical prediction rules useful in predicting resilience in older multiple myeloma patients undergoing chemotherapy. The PESC impacts public health by performing studies that develop knowledge to maintain or recover independence in older Americans, by promoting reserve and resilience in the face of chronic and acute stressors.